This proposal requests funds for the purchase of a new microcapillary HPLC nanoflow rate electrospray tandem quadrupole orthogonal- acceleration time-of-flight mass spectrometer (Q-STAR). This shared instrument will be used for structural studies of bio-macromolecules and their myriad covalent modifications that are of critical importance to on- going research in the biological and medical sciences in the San Francisco Bay Area. It will be housed in the NIH NCRR-supported Mass Spectrometry Resource at UCSF. This environment ensures the availability of the scientific, technical and management expertise required to optimize its productivity in solving problems at the forefront of macromolecular biology and medicine for a large number of investigators. The proposed instrumentation will provide high precision, accurate mass CID spectra at high absolute sensitivity from on-line microcapillary separations and sequence analyses of protein digests at the femtomole level. This powerful capability is currently unavailable to these investigators. The major users are a group of 17 scientists and clinicians involved in over 31 NIH-supported research programs. These investigators have established needs for protein identification and identification of phosphorylation sites and other protein modifications that will be met with the proposed new instrument system These research projects are at the forefront of biomedical problems involving natural and aberrant proteins required in deciphering cell function and dysfunction, respectively. Most of these studies require the high absolute sensitivity and precision performance of the instrument requested. Prof. Keith Yamamoto will chair the Advisory Committee responsible for the overall guidance of the shared instrument's use. The committee will assure that the time is shared equitably and that some 10% of its time will be made available to other projects requiring its unique capability. The UCSF Academic Senate's Committee on Research and the primary users will contribute $45,162 toward this purchase. Mr. David Maltby, who has extensive experience in electrospray and other types of biological mass spectrometry, will oversee scheduling, training and maintenance and will provide daily supervision of usage. Long term productive usage and maintenance will be assured by the close association with a major Mass Spectrometry Facility and financial support of the major users.